Neuropathic Pain in Multiple Sclerosis and Its Animal Models: Focus on Mechanisms, Knowledge Gaps and Future Directions

Abstract

Multiple sclerosis (MS) is a multifaceted, complex and chronic neurological disease that leads to motor, sensory and cognitive deficits. MS symptoms are unpredictable and exceedingly variable. Pain is a frequent symptom of MS and manifests as nociceptive or neuropathic pain, even at early disease stages. Neuropathic pain is one of the most debilitating symptoms that reduces quality of life and interferes with daily activities, particularly because conventional pharmacotherapies do not adequately alleviate neuropathic pain. Despite advances, the mechanisms underlying neuropathic pain in MS remain elusive. The majority of the studies investigating the pathophysiology of MS-associated neuropathic pain have been performed in animal models that replicate some of the clinical and neuropathological features of MS. Experimental autoimmune encephalomyelitis (EAE) is one of the best-characterized and most commonly used animal models of MS. As in the case of individuals with MS, rodents affected by EAE manifest increased sensitivity to pain which can be assessed by well-established assays. Investigations on EAE provided valuable insights into the pathophysiology of neuropathic pain. Nevertheless, additional investigations are warranted to better understand the events that lead to the onset and maintenance of neuropathic pain in order to identify targets that can facilitate the development of more effective therapeutic interventions. The goal of the present review is to provide an overview of several mechanisms implicated in neuropathic pain in EAE by summarizing published reports. We discuss current knowledge gaps and future research directions, especially based on information obtained by use of other animal models of neuropathic pain such as nerve injury.

Neurological Benefits, Clinical Challenges, and Neuropathologic Promise of Medical Marijuana: A Systematic Review of Cannabinoid Effects in Multiple Sclerosis and Experimental Models of Demyelination

“…MS patients manifest a range of symptoms [5] as a result of motor, sensory, autonomic, and psycho-behavioral dysfunction including fatigue (75-90%) and mobility impairment (90%) [6], gait difficulties [7], paresthesia [8], vision problems [9,10], speech impairments [11,12], dizziness and vertigo [13], urinary bladder dysfunction [14,15], neurogenic bowel dysfunction [16], sexual dysfunction [17], chronic neuropathic pain (85%) [18], cognitive deficits in information processing, speed, episodic memory, complex attention and executive function [19][20][21], physical disability [22], anxiety and depression [23], and sleep disturbances that correlate with fatigue and depression [24][25][26].…”

Lower corticospinal excitability and greater fatigue among people with multiple sclerosis experiencing pain

“…Interhemispheric differences in TMS measures from the weaker versus stronger sides in MS mirror hand dominance in healthy controls. 33 – 35 Neuropathic pain in MS is associated with corresponding limb weakness, 36 and the painful weaker limb in other pain research shows corresponding corticospinal excitability abnormalities. 37 In MS, the hemisphere of the weaker hand has lower corticospinal excitability and higher corticospinal inhibition than the stronger side.…”

Розсіяний Склероз Та Біль

“…населення, і цей показник підвищується в середньому на 1000-1200 осіб щороку. РС -невиліковне захворювання, тому метою терапевтичних методів є сповільнення прогресування хвороби і зменшення вираженості симптомів для покращання якості життя пацієнтів [1][2][3][4].…”

“…Типовими клінічними проявами РС є двоїння в очах, рухові розлади (геміпарез, парапарез), координаторні розлади (атаксія), порушення функції тазових органів (найчастіше затримка, нетримання сечі або імперативні поклики до сечовипускання) [1][2][3][4]. Біль -частий симптом у пацієнтів із РС, якому клініцисти зазвичай приділяють недостатньо уваги.…”